(2R, 4S, 5S) 1-(4-(4-(((7-Chloroquinolin-4-yl)amino)methyl)-1H-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

Round 1

Reviewer 1 Report

In order for the manuscript to be published, it needs to be revised according to the following comments.

Figure 1: error in formula g.

Figure 1, Scheme 1: In the furan ring of compounds 1 and 4, according to their formulas, the configuration on stereogenic centers is 2R,4S,5S, while in the name of compound 4 given on lines 2-4, 73-74 and in the Supplementary Material, the configuration on the stereogenic centers is not expressed.

Line 75: wrong name of compound 3.

Line 107: The term "olefinic methylene" makes no sense.

Lines 113-115: The UV spectrum comment is laconic. The correct term is absorption band, not peak.

Line 118: Figure S14a is incorrectly listed instead of Figure S15a.

Line 120: It is not clear why the stretching vibration of the azido group is assigned to the absorption band at 2113 cm^–1 and what the absorption band at 2079 cm^–1 belongs to.

Lines 176-177: The mass of propargylamine should also be given, while "4 equiv" is unnecessary.

Line 184: Melting point is missing, yield is given in duplicate.

All ¹H chemical shits to two decimal places and all ¹³C chemical shits to one decimal place (for example, 32.0) must be reported everywhere in the manuscript and in the Supplementary Material.

Supplementary material should be edited so that each heading is on the same page as the object to which it relates. The placement of the formula in front of Table S1 needs to be adjusted so that it can be seen in its entirety.

Ref. 1: Before the link, it is necessary to add what it is about (website of World Health Organization). The day of accession should be indicated after the line, not just the year.

Journal publications should be cited with the names of all authors.

Author Response

15 June 2023

Editor

Molbank

Dear Editor,

Enclosed please find the manuscript revised version of an original research article entitled " (2R, 4S, 5S) 1-(4-(4-(((7-chloroquinolin-4-yl)amino)methyl)-1H-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione" by Hou In Kuan, Yuhan Xie , Yuzhu Guo, Alessandra Gianoncelli, Giovanni Ribaudo and Paolo Coghi for your consideration. We prepared this improved version following the comments that we received from the Reviewer. The modified parts have been highlighted in the files, and we reported a list of changes below.

We believe that this manuscript would be suitable for publication as an original research article in Molbank.

______________________

Dr. Paolo Coghi, Ph.D

Corresponding Authors: Dr. Giovanni Ribaudo, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy and Dr. Paolo Coghi, School of Pharmacy, Macau University of Science and Technology, Macau, China Tel: +853-88972853 (PC)

E-mail address: giovanni.ribaudo@unibs.it  (GR);coghips@must.edu.mo (PC)

In order for the manuscript to be published, it needs to be revised according to the following comments.

We would like to thank the Reviewer for comments that we received and that were very useful to improve the quality of our paper.

Figure 1: error in formula g.

Thanks for the comment. Figure 1 was corrected accordingly.

Figure 1, Scheme 1: In the furan ring of compounds 1 and 4, according to their formulas, the configuration on stereogenic centers is 2R,4S,5S, while in the name of compound 4 given on lines 2-4, 73-74 and in the Supplementary Material, the configuration on the stereogenic centers is not expressed.

Thanks for the comment. We have added the stereogenic centers as requested.

Line 75: wrong name of compound 3.

Thanks for the comment. The name has been corrected.

Line 107: The term "olefinic methylene" makes no sense.

We modified this part as in the following: “[…] classified by DEPT experiments as one methyl group, three methylene, five methine, five aromatic, and eight quaternary carbons”.

Lines 113-115: The UV spectrum comment is laconic. The correct term is absorption band, not peak.

Thanks for this comment, we apologize for the mistake. Accordingly, lines 113-115 were updated and the term “absorption peak” was introduced.

Line 118: Figure S14a is incorrectly listed instead of Figure S15a.

We apologize for this typo. This part was corrected following this observation.

Line 120: It is not clear why the stretching vibration of the azido group is assigned to the absorption band at 2113 cm^–1 and what the absorption band at 2079 cm^–1 belongs to.

We thank the Reviewer for having raised this point. We compared our experimental results with literature data.

As indicated in:

• Essa, A.H.; Ibrahim, M.; Hameed, A.J.; AI-Masoudi, N. A. Theoretical investigation of 3’-substituted -2’-3’-dideoxythymidines related to AZT. QSAR infrared and substituent electronic effect studies. ARKIVOC 2008, viii, 255-265
• Araújo, A. A., Storpirtis, S., Mercuri, L. P., Carvalho, F. M., dos Santos Filho, M., & Matos, J. R. (2003). Thermal analysis of the antiretroviral zidovudine (AZT) and evaluation of the compatibility with excipients used in solid dosage forms. International journal of pharmaceutics, 260(2), 303–314. https://doi.org/10.1016/s0378-5173(03)00288-6

the stretching band of N=N=N in AZT is 2103 cm-1, very similar to our data (2113 cm-1).

In the paper:

• Gai XS, Coutifaris BA, Brewer SH, Fenlon EE. A direct comparison of azide and nitrile vibrational probes. Phys Chem Chem Phys. 2011 Apr 7;13(13):5926-30. doi: 10.1039/c0cp02774j

the stretching band of N=N=N in AZT is reported at 2113 cm-1.

Lines 176-177: The mass of propargylamine should also be given, while "4 equiv" is unnecessary.

We thank the Reviewer for this comment. This has been corrected.

Line 184: Melting point is missing, yield is given in duplicate.

Thanks for the comment. This has been corrected.

All ¹H chemical shits to two decimal places and all ¹³C chemical shits to one decimal place (for example, 32.0) must be reported everywhere in the manuscript and in the Supplementary Material.

We apologize for this error. We are grateful for this comment, we have corrected this mistake.

Supplementary material should be edited so that each heading is on the same page as the object to which it relates. The placement of the formula in front of Table S1 needs to be adjusted so that it can be seen in its entirety.

We are grateful for these suggestions. The supplementary file has been modified accordingly.

Ref. 1: Before the link, it is necessary to add what it is about (website of World Health Organization). The day of accession should be indicated after the line, not just the year.

Thanks for comment, we introduced the requested modifications.

Journal publications should be cited with the names of all authors.

Thanks for the comment. References have been corrected.

Author Response File: Author Response.docx